Biomedical subjects

A Mendrek

Publications and source records attributed to A Mendrek.

9 recordsLinked to original sources

PubMed2005

Dysfunction of a distributed neural circuitry in schizophrenia patients during a working-memory performance.

BACKGROUND: In a recent longitudinal study of first-episode schizophrenia patients, we found that while dysfunction of the right dorsolateral prefrontal cortex (DLPFC), right thalamus, left cerebellum and cingulate gyrus normalized with antipsychotic treatment and significant reduction in symptomatology, the left DLPFC, left thalamus, and right cerebellum remained disturbed. In the present study we investigated whether these abnormalities are also present in clinically stable, relatively well-functioning schizophrenia patients in comparison to control subjects during performance of the N-back working-memory task. METHOD: Twelve schizophrenia and 12 control subjects completed the study. The functional images collected during scanning were analyzed using a random-effects model in a restricted set of six regions of interest (ROIs). In addition, the exploratory search in the entire brain volume was performed. RESULTS: The ROI analyses revealed relative underactivation in the region of the left DLPFC and the right cerebellum, as well as overactivation in the left cerebellum. The exploratory whole-brain search exposed additional overactivation in the medial frontal, anterior cingulate, and left parietal cortices. CONCLUSIONS: The present study provides evidence of significant underactivations in stable schizophrenia patients in regions that we have previously observed to be dysfunctional in acutely psychotic and partially remitted patients, together with extensive overactivations in several regions that potentially reflect some compensatory mechanism or increased effort on the working-memory task.

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PubMed2004

Changes in distributed neural circuitry function in patients with first-episode schizophrenia.

BACKGROUND: A number of functional brain abnormalities have been reported in schizophrenia, but it remains to be determined which of them represent trait and state markers of the illness. AIMS: To delineate regional brain dysfunctions that remain stable and those that fluctuate during the course of schizophrenia. METHOD: A cohort of patients with first-episode schizophrenia and a matched group of control participants underwent functional magnetic resonance imaging on two occasions 6-8 weeks apart during performance of a working memory task. The patients' disease was in partial remission at the second scan. RESULTS: Relative to control participants, the function of the left dorsolateral prefrontal cortex, left thalamus and right cerebellum remained disturbed in the people with schizophrenia, whereas the dysfunction of the right dorsolateral prefrontal cortex, right thalamus, left cerebellum and cingulate gyrus normalised, with significant reduction in symptoms. CONCLUSIONS: These results suggest that dysfunction of the left fronto-thalamo-cerebellar circuitry is a relatively stable characteristic of schizophrenia, whereas disturbance of the right circuitry and cingulate gyrusis predominantly a state-related phenomenon.

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PubMed2001

Limbic abnormalities in affective processing by criminal psychopaths as revealed by functional magnetic resonance imaging.

BACKGROUND: Psychopathy is a complex personality disorder of unknown etiology. Central to the disorder are anomalies or difficulties in affective processing. METHODS: Functional magnetic resonance imaging was used to elucidate the neurobiological correlates of these anomalies in criminal psychopaths during performance of an affective memory task. RESULTS: Compared with criminal nonpsychopaths and noncriminal control participants, criminal psychopaths showed significantly less affect-related activity in the amygdala/hippocampal formation, parahippocampal gyrus, ventral striatum, and in the anterior and posterior cingulate gyri. Psychopathic criminals also showed evidence of overactivation in the bilateral fronto-temporal cortex for processing affective stimuli. CONCLUSIONS: These data suggest that the affective abnormalities so often observed in psychopathic offenders may be linked to deficient or weakened input from limbic structures.

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PubMed1999

Neural pathways involved in the processing of concrete and abstract words.

The purpose of this study was to delineate the neural pathways involved in processing concrete and abstract words using functional magnetic resonance imaging (fMRI). Word and pseudoword stimuli were presented visually, one at a time, and the participant was required to make a lexical decision. Lexical decision epochs alternated with a resting baseline. In each lexical decision epoch, the stimuli were either concrete words and pseudowords, or abstract words and pseudowords. Behavioral data indicated that, as with previous research, concrete word stimuli were processed more efficiently than abstract word stimuli. Analysis of the fMRI data indicated that processing of word stimuli, compared to the baseline condition, was associated with neural activation in the bilateral fusiform gyrus, anterior cingulate, left middle temporal gyrus, right posterior superior temporal gyrus, and left and right inferior frontal gyrus. A direct comparison between the abstract and concrete stimuli epochs yielded a significant area of activation in the right anterior temporal cortex. The results are consistent with recent positron emission tomography work showing right hemisphere activation during processing of abstract representations of language. The results are interpreted as support for a right hemisphere neural pathway in the processing of abstract word representations.

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PubMed1999

Discriminant cognitive factors in responder and non-responder patients with schizophrenia.

UNLABELLED: To identify which improvements in cognitive function are associated with symptom resolution in schizophrenic patients treated with atypical antipsychotics. DESIGN: a prospective open trial with atypical neuroleptics (risperidone, clozapine, quetiapine). SETTING: Inpatient and outpatient units, Institute of Psychiatry. PATIENTS: Thirty-nine patients with schizophrenia according to DSM-IV criteria were included. Clinical and cognitive assessment were done at baseline (T0) and again after six months of treatment (T2). Twenty-five patients completed the trial. INTERVENTIONS: New-generation antipsychotics during six months. Patients were considered as responders if their PANSS score decreased at least 20% (n = 15) and non-responders if it did not (n = 10). OUTCOME MEASURES: a computerized cognitive assessment comprised tests of short-term-memory (digit span), explicit long-term memory (word pair learning), divided attention, selective attention and verbal fluency (orthographic and semantic). Clinical assessment included PANSS and ESRS. RESULTS: A discriminant function analysis was performed to determine which changes in cognitive performance predicted symptomatic response status. Semantic fluency and orthographic fluency were significant predictors. Together they correctly predicted responder status in 88% of cases. Memory was not a significant predictor of symptomatic response. CONCLUSION: Verbal fluency discriminated the responder from the non-responder group during a pharmacological treatment.

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PubMed1998

Pre-exposure of rats to amphetamine sensitizes self-administration of this drug under a progressive ratio schedule.

Two groups of male rats were tested to determine whether pre-exposure to d-amphetamine would enhance the motivation to self-administer the drug under a progressive ratio schedule of reinforcement. In the first phase of the experiment, one group of rats received d-amphetamine (2 mg/kg IP), while a second group received saline on alternate days for a total of ten injections. Following a 21-day drug withdrawal period, behavioral sensitization was confirmed by a significant increase in amphetamine-induced stereotypy in the d-amphetamine-pretreated group, relative to the saline-pretreated group. In the second phase of the study, all rats were implanted with chronic jugular catheters and trained to self-administer d-amphetamine (0.2 mg/kg per infusion) under a fixed-ratio schedule of reinforcement. The progressive ratio paradigm was then imposed for 7 consecutive days; d-amphetamine-pretreated rats attained significantly higher break points than saline-pretreated animals. These data suggest that pre-exposure to d-amphetamine may enhance the motivation to self-administer this drug.

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PubMed1996

MK-801 (dizocilpine): synergist and conditioned stimulus in bromocriptine-induced psychomotor sensitization.

Intraperitoneal injections of the D2/D3 dopamine agonist bromocriptine (5.0 mg/kg, IP) induced locomotion that became progressively stronger on successive days of testing. The sensitized response developed twice as rapidly when the non-competitive NMDA antagonist MK-801 (0.25 mg/kg, IP) was given 30 min after bromocriptine (so that the peak effects of the two drugs overlapped). In a second group of animals, MK-801 was given 30 min prior to bromocriptine (the pretreatment regimen typical of studies where MK-801 is reported to block cocaine, amphetamine or morphine sensitization) and locomotion was monitored during the pretreatment period; in this case sensitization to the locomotor-stimulating effects of MK-801 alone (in the pretreatment period) as well as sensitization to the locomotor-stimulating effects of the drug combination (following the second injection) were observed. No sensitization to the effects of MK-801 alone (pretreatment) were seen in animals that received saline rather than bromocriptine as their second injection in this experiment. Thus MK-801 does not block but rather enhances bromocriptine sensitization; it appears to do so by a synergism with the locomotor effects of bromocriptine and by becoming a conditioned stimulus for the sensitized response. These findings confirm the earlier report that NMDA receptor activation is not critical to bromocriptine-induced sensitization, and they illustrate the importance of controls for conditioning and state-dependency phenomena in studies of drug interactions in psychomotor sensitization.

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PubMed1995

MK-801 disrupts the expression but not the development of bromocriptine sensitization: a state-dependency interpretation.

Repeated administration of the D2-type agonist bromocriptine (5.0 mg/kg, IP) caused progressive increases in the locomotor-stimulating effects of the drug in rats. Similar progressive increases in locomotor activity were observed in rats that received repeated coadministration of the NMDA receptor antagonist MK-801 (0.25 mg/kg, IP) plus bromocriptine. However, when rats previously treated with the combination of drugs received either bromocriptine or MK-801 alone, their levels of activity were comparable to those of rats having no prior experience with either drug. A second group of rats was sensitized to the effects of bromocriptine alone; no evidence of bromocriptine sensitization was seen when MK-801 was subsequently coadministered with bromocriptine. Thus, either the presence or the absence of MK-801 could--depending upon the conditions of previous drug treatment--block the expression of bromocriptine sensitization. When a third group of rats was sensitized to the combination of MK-801 plus bromocriptine and subsequently tested following 2 or 6 drug-free weeks, evidence of sensitized responses was still present. Thus, at the very least, blockade of NMDA receptors with MK-801 fails to compromise the cellular changes associated with sensitization to the repeated combination of MK-801 plus bromocriptine. Bromocriptine sensitization may prove to be unique in this regard, but the present findings suggest a control condition that should be carefully explored in studies of the effects of MK-801 on sensitization involving other stimulant drugs.

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PubMedDate not supplied

[Effects of listening to previously hallucinated words by schizophrenia patients in remission: a functional magnetic resonance imaging study of six cases].

BACKGROUND: Despite immense importance of auditory verbal hallucinations (AVHs) in the phenomenology of schizophrenia, the neurocognitive and neurophysiological bases of AVHs remain obscure. On the neurocognitive level, it has been proposed that AVHs arise from the disordered monitoring manifested by patients' inability to recognize their inner speech as being their own. On the neurophysiological level, the AVHs have been attributed to the aberrant activity in the primary auditory cortex (Heschl's gyrus). Although interesting, these models cannot account for the very specific and restricted content of AVHs in individual patients. The specific content of AVHs persists across different psychotic episodes even after extended periods of remission. Furthermore, the AVHs are usually triggered by emotionally charged and stressful situations. DESIGN: We hypothesized that even during absence of AVHs, when patients are in remission, the verbal content remains present in the latent, pre-clinical form. In order to elucidate potential cerebral substrates of the dormant AVHs content, we employed functional magnetic resonance imaging (fMRI) in 6 schizophrenia patients in total remission of AVHs for at least 12 months, during listening to the words hallucinated by them in the past. Specifically, we created the list of previously hallucinated words for each patient and matched the words in terms of length, structure, emotional valence, semantic category and frequency of usage with the non-hallucinated words. Moreover, each patient was paired demographically with the control participant who was presented with the same words. We predicted that exposure to the hallucinated versus non-hallucinated words would result in increased activation in cerebral areas associated with cognitive and emotional content of previously experienced AVHs in patients, whereas the same comparison will not produce any significant changes in blood oxygen level-dependent (BOLD) signal in control participants. In addition, based on existing neuroimaging data obtained during experience of AVHs, we hypothesized that previously hallucinated words may elicit greater activation in the primary auditory cortex than the non-hallucinated words in patients. Each pair of participants was analyzed separately. RESULTS: The most consistent finding in patients, absent in all control participants, was significant activation in the orbitofrontal and medial prefrontal cortex (PFC) during listening to previously hallucinated versus non-hallucinated words. The orbitofrontal and medial PFC are both part of corticolimbic system and play an important role in cognitive control of emotion processing. DISCUSSION: Thus, present results imply that previously hallucinated words, even in remission, are associated with inappropriate emotional response on neurophysiological level in schizophrenia patients. The relative hyperactivation of orbitofrontal and medial PFC in patients may stem from and/or may contribute to anomalous neural plasticity and disordered connectivity in the corticolimbic circuitry. This in turn could lead to attribution of excessive emotional salience to normally neutral stimuli and over time via process of sensitization could result in hallucinations. Potential normalization of this dysfunction could reduce patients' susceptibility to experience AVHs in stressful situations. In addition to observed hyperactivations in the PFC, some schizophrenia patients exhibited anomalous BOLD signal in other regions of the corticolimbic system such as anterior cingulate gyrus and parahippocampal gyrus. These additional anomalies could be related to greater affective sensitivity to the hallucinated versus non-hallucinated words in some patients. CONCLUSION: Finally, in contrast to our initial hypothesis we did not observe any significant differences between processing of the hallucinated versus non-hallucinated words in the primary auditory cortex. In retrospect, this result is not surprising because patients did not experience internally generated AVHs while in the scanner, but instead were exposed exclusively to externally generated stimuli.

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